title: Profiling of Glucose-Sensing Neurons Reveals that GHRH Neurons Are Activated by Hypoglycemia.
abstract: Comprehensive transcriptional profiling of glucose-sensing neurons is challenging because of low expression levels of glucokinase (Gck) and other key proteins that transduce a glucose signal. To overcome this, we generated and validated transgenic mice with a neuronal/endocrine-specific Gck promoter driving cre expression and mated them to mice with cre-dependent expression of an EGFP-tagged ribosomal protein construct (EEF1A1-LSL.EGFPL10) that can be used to map and profile cells. We found significant Gck expression in hypothalamic and limbic regions in cells that are activated following administration of glucose or 2-deoxyglucose. Transcriptional profiling from Gck-cre/EEF1A1-LSL.EGFPL10 mice enriched known and previously unknown glucose-sensing populations including neurons expressing growth hormone releasing hormone (GHRH). Electrophysiological recordings show that hypoglycemia activates GHRH neurons, suggesting a mechanistic link between hypoglycemia and growth hormone release. These studies provide a means for mapping glucose-sensitive neurons and for generating transcriptional profiles from other cell types expressing cre in a cell-specific manner.
authors.affiliation: Laboratory of Molecular Genetics, Rockefeller University, New York, NY 10065, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Stanley
authors.forename: Ana I
authors.initials: AI
authors.lastname: Domingos
authors.forename: Leah
authors.initials: L
authors.lastname: Kelly
authors.forename: Alastair
authors.initials: A
authors.lastname: Garfield
authors.forename: Shadi
authors.initials: S
authors.lastname: Damanpour
authors.forename: Lora
authors.initials: L
authors.lastname: Heisler
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Friedman
mesh_terms: D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology; D020869:Gene Expression Profiling; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D007003:Hypoglycemia / Q000378:metabolism / Q000473:pathology; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D012269:Ribosomal Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D013007:Growth Hormone-Releasing Hormone; D003847:Deoxyglucose; D005941:Glucokinase; D005947:Glucose